Basal rate testing using frequent blood glucose input

ABSTRACT

An apparatus comprising a user interface configured to generate an electrical signal to start a basal insulin rate test when prompted by a user, an input configured to receive sampled blood glucose data of a patient that is obtained during a specified time duration, including a time duration during delivery of insulin according to a specified basal insulin rate pattern, and a controller communicatively coupled to the input and the user interface. The controller includes an insulin calculation module configured for determining at least one of an amount of basal insulin over-delivered and an amount of basal insulin under-delivered during the basal insulin rate test in trying to meet a target blood glucose baseline. Other devices and methods are disclosed.

RELATED APPLICATION

This application is a continuation of U.S. application Ser. No.15/266,468 filed Sep. 15, 2016, which is a continuation of U.S.application Ser. No. 11/685,617 filed Mar. 13, 2007, which are herebyfully incorporated herein by reference.

TECHNICAL FIELD

The field generally relates to patient insulin management devices and,in particular, but not by way of limitation, to systems, devices andmethods for adjusting insulin therapy.

BACKGROUND

People who suffer from diabetes require insulin to keep their bloodglucose level as close as possible to normal levels. It is essential forpeople with diabetes to manage their blood glucose level to within anormal range. Complications from diabetes can include heart disease(cardiovascular disease), blindness (retinopathy), nerve damage(neuropathy), and kidney damage (nephropathy). Insulin is a hormone thatreduces the level of blood glucose in the body. Normally, insulin isproduced by beta cells in the pancreas. In non-diabetic people, the betacells release insulin to satisfy two types of insulin needs. The firsttype is a low-level of background insulin that is released throughoutthe day. The second type is a quick release of a higher-level of insulinin response to eating. Insulin therapy replaces or supplements insulinproduced by the pancreas.

Conventional insulin therapy typically involves one or two injections aday. The low number of injections has the disadvantage of allowinglarger variations in a person's insulin levels. Some people withdiabetes manage their blood glucose level with multiple daily injections(MDI). MDI may involve more than three injections a day and four or moreblood glucose tests a day. MDI offers better control than conventionaltherapy. However, insulin injections are inconvenient and require adiabetic person to track the insulin doses, the amount of carbohydrateseaten, and their blood glucose levels among other information criticalto control.

Blood glucose (BG) management devices help a diabetic person managetheir blood glucose. For example, an insulin pump is a BG managementdevice that provides insulin throughout the day. A glucose monitor (GM)or meter is a BG management device that measures blood glucose levels.Some GMs require a finger-stick to acquire a sample of blood that isapplied to a test strip to get a blood glucose reading. Some GMs areable to provide continuous monitoring of blood glucose. Other BGmanagement devices include computers running software to help a diabeticperson manage insulin therapy. However, most BG management devices arelimited in the control over blood glucose that they offer.

SUMMARY

This document discusses, among other things, devices and methods formanaging insulin therapy. A device example includes a user interfaceconfigured to generate an electrical signal to start a basal insulinrate test when prompted by a user, an input configured to receivesampled blood glucose data of a patient that is obtained during aspecified time duration, including a time duration during delivery ofinsulin according to a specified basal insulin rate pattern, and acontroller communicatively coupled to the input and the user interface.The controller includes an insulin calculation module configured fordetermining at least one of an amount of basal insulin over-deliveredand an amount of basal insulin under-delivered during the basal insulinrate test in trying to meet a target blood glucose baseline.

A method example includes receiving a user prompt in a blood glucose(BG) management device to start a basal insulin rate test, receivingsampled blood glucose data that is obtained during a specified durationof time when insulin is delivered according to a specified basal insulinrate pattern, and determining at least one of an amount of basal insulinover-delivered and an amount of basal insulin under-delivered in tryingto meet a target blood glucose baseline during the basal insulin ratetest using the BG management device.

This summary is intended to provide an overview of the subject matter ofthe present patent application. It is not intended to provide anexclusive or exhaustive explanation of the invention. The detaileddescription is included to provide further information about the subjectmatter of the present patent application.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a block diagram of portions of a BG management device.

FIG. 2 shows example illustrations of a blood glucose concentrationgraph and a basal rate pattern.

FIG. 3 is a block diagram of portions of an example of a BG managementdevice that includes a pump mechanism.

FIG. 4 is an illustration of a BG management device that includes aninsulin pump.

FIG. 5 is another block diagram of portions of a BG management devicethat includes a pump mechanism.

FIG. 6 is a block diagram of a BG management device that includes ablood glucose sensor circuit.

FIG. 7 is a block diagram of portions of another example of a BGmanagement device.

FIG. 8 is a flow diagram of a method of using a BG management device toexecute a basal rate test.

FIG. 9 is a flow diagram of another method of using a BG managementdevice to execute a basal rate test.

DETAILED DESCRIPTION

In the following detailed description, reference is made to theaccompanying drawings which form a part hereof, and specific embodimentsin which the invention may be practiced are shown by way ofillustration. It is to be understood that other embodiments may be usedand structural or logical changes may be made without departing from thescope of the present invention.

It is important for a diabetic person to be treated with the properamount of insulin. As discussed previously, high blood sugar can lead toserious complications. Conversely, a person with low blood sugar candevelop hypoglycemia. Ideally, insulin therapy mimics the way the bodyworks. An insulin pump is one way to mimic the body's insulinproduction. An insulin pump can provide a background or basal infusionof insulin throughout the day and provide a quick release or bolus ofinsulin when carbohydrates are eaten. If a person develops high bloodsugar, a correction bolus can be delivered by the pump to correct it.While insulin pumps improve convenience and flexibility for a diabeticperson, they can be sophisticated devices. Some insulin pumps can bedifficult to program. Proper use of an insulin pump requires a user togo through a learning curve to properly use and program the pump.

Basal rate refers to a type of twenty-four hour background infusion ofinsulin by an insulin pump that mimics the continuous background releaseof insulin from a normal pancreas. It is the rate of insulin deliverythe patient normally needs independent of the consumption of meals. Thebasal rate is typically specified in insulin units per hour (u/hr).Typically, a basal rate for a pump is initially programmed by aclinician based on a total daily dose (TDD) of insulin for a diabeticperson. The clinician may determine TDD based on many factors includingthe type of diabetes of the patient and the patient's weight, age, andlevel of fitness. The amount of basal insulin is typically determined tobe a percentage of TDD, such as 40%, 50%, or 60% for example. The totaldaily dose is then divided by 24 to obtain an average basal rate. Forexample, if a patient's TDD is determined to be 40 units of insulin, and50% of the TDD is used for basal delivery, the average basal rate is 20units/24 hours or 0.83 u/hr.

Many insulin pump users may use three or more different basal ratesduring the course of a day. Basal rates can be adjusted to changedelivery every few minutes (e.g., 20-30 minutes) by increments as smallas 0.05 u/hr to better track changes in demand, such as from an increasetypically needed before dawn or a decrease needed during long activeperiods. Insulin pump users may use different basal rates for overnight,for breakfast to mid-afternoon, and for mid-afternoon to bedtime.Appropriate basal rates vary from person to person, may be different fora person at various times of the day, and may change for a person overtime. Inappropriate basal rate settings may result in low blood glucoselevels overnight or high blood glucose levels in the morning. An insulinpump user may go through several iterations of trial and error beforefinding appropriate basal rates. Because a patient's basal insulin needsmay change over time, such as with weight change or with a change infitness level, basal rate testing may be performed periodically toensure that an appropriate basal rate is being delivered by an insulinpump. Blood glucose (BG) management devices are more valuable to adiabetic person if the device conveniently assists them in determiningtheir appropriate basal rate or rates.

Apparatus Embodiments

FIG. 1 is a block diagram of portions of a BG management device 100.Examples of a BG management device 100 include, among other devices, aninsulin pump, a blood glucose monitor (GM) or meter, and a computingdevice running software to assist a diabetic patient in managing insulintherapy. Examples of a computing device include, among other things, apersonal computer or a personal data assistant (PDA).

The BG management device 100 includes a user interface 105, an input110, and a controller 115 communicatively coupled to the input 110 andthe user interface 105. The controller 115 can be implemented usinghardware circuits, firmware, software or any combination of hardware,firmware and software. Examples, include a microcontroller, a logicalstate machine, and a processor such as a microprocessor, applicationspecific integrated circuit (ASIC), or other type of processor.

The user interface 105 generates an electrical signal to begin a basalrate test when prompted by a user. The user interface 105 may include apushbutton, keypad, or a computer mouse. The user interface 105 mayinclude a display operatively coupled to the controller 115 to providepatient or user instructions for the basal rate test. Examples ofinstructions include, among other things, instructing the patient not toeat during the test, to maintain a normal activity level, and not toadminister an insulin correction bolus during the test. The display mayinclude a touch-screen. The user of the device may be a clinician,caregiver, or a diabetic patient. The user prompts the BG managementdevice 100 using the user interface 105 to begin a basal rate test. Thebasal rate test assists the user in determining one or more appropriatebasal rates.

As part of a basal rate test, the patient receives insulin according toa specified basal rate pattern or profile. If the BG management device100 includes an insulin pump, the basal insulin may be delivered usingthe BG management device 100. If the BG management device 100 does notinclude an insulin pump, the basal insulin may be delivered using aseparate device that includes an insulin pump.

If the BG management device 100 includes an insulin pump, the BGmanagement device 100 may further include a memory 116 to store at leastone basal rate pattern. The controller 115 may display instructions forthe user to enter one or more basal rates to be delivered according totime of day. For example, the BG management device 100 may allow theuser to enter basal rate values in 0.05 u/hr increments, and to entertime in increments of one-half hour throughout the day. In someembodiments, the BG management device 100 stores different basal ratepatterns according to different segments of the day, such as early inthe day, late in the day, and overnight for example. In someembodiments, the input 110 may include a communication port and a basalrate pattern may be loaded from a second device into memory 116.

The input 110 is configured to receive sampled blood glucose data of thepatient as part of the basal rate test. The blood glucose data providesan indication of the concentration level of the patient's blood sugarand the data may be obtained from blood directly or from insterstitialfluid. The blood glucose data is obtained during a specified timeduration. The specified time duration includes a time when insulin isdelivered according to a specified basal rate pattern, but may include atime prior or after the delivery of insulin as well. The configurationof the input 110 may depend on the type of BG management device 100. Ifthe BG management device 100 is an insulin pump, the input 110 may becoupled to a GM included in the pump or the input 110 may include acommunication port to receive the blood glucose data from a seconddevice. The second device may include a GM or the second device mayreceive the blood glucose data from a third device. In some embodiments,the input 110 is coupled to the user interface 105, and the user maymanually input the data into the pump through a keypad or keyboardincluded in the user interface.

The controller 115 includes an insulin calculation module 120. Modulescan be software, hardware, firmware or any combination of software,hardware, and firmware. Multiple functions can be performed in one ormore modules. The insulin calculation module 120 determines at least oneof an amount of basal insulin over-delivered and an amount of basalinsulin under-delivered during the basal insulin rate test in trying tomeet a target blood glucose baseline.

FIG. 2 shows example illustrations (not real data) of a blood glucoseconcentration graph 205 and a basal rate pattern 220 or profile during abasal rate test. Assume, as shown in the blood glucose concentrationgraph 205, that the patient's target blood glucose baseline 215 is 150mg/dl (milligrams per deciliter) and that this is the patient's bloodglucose concentration level before the basal rate test. Basal insulin isbeing delivered according to a basal rate pattern 220. At time t₀, theuser elects to begin a basal rate test. User instructions for the basalrate test may be provided. The blood glucose concentration is determinedfrom blood glucose data received into the input 110 during the basalrate test. The basal rate test may run over several hours, e.g., six toeight hours. In some embodiments, the blood glucose data may be storedin memory for processing. In some embodiments, the blood glucose datamay be processed by the insulin calculation module 120 as it isreceived.

If the patient's blood glucose level remains at the target blood glucosebaseline 215 or within a specified range of the target blood glucosebaseline 215, the basal profile is appropriate. If the patient's bloodglucose level rises above the target blood glucose baseline 215 or risesabove a specified range of the target blood glucose baseline 215, thebasal rate is too low and there was an under-delivery of basal insulin.If the patient's blood glucose level falls below the target bloodglucose baseline 215 or falls below a specified range of the targetblood glucose baseline 215, the basal rate is too high and there was anover-delivery of basal insulin.

In the example in FIG. 2, the patient's blood glucose begins to rise attime t₃. The change in the blood glucose from the baseline reaches 190mg/dl, or an increase of 40 mg/dl. At time t₄, the basal rate pattern220 includes an increase in basal rate. The blood glucose level of thepatient begins to change direction, here a decrease, at time t₅. Thetime duration from the increase at t₃ to the change in direction at ist₅ about two hours in this example. The blood glucose level of thepatient eventually falls to 110 mg/dl, or a total decrease of 80 mg/dl.At time t₇, the blood glucose level of the patient begins to againchange direction. This time the change in direction is an increase inblood glucose concentration. The time duration from the decrease at t₅to the change in direction at t₇ is about six hours.

In some embodiments, the insulin calculation module 120 is configured todetermine the over-delivered amount or the under-delivered amount ofbasal insulin using a correction factor of the patient and a variance ofa blood glucose level from the target blood glucose baseline 215. Acorrection factor refers to the amount of drop in blood glucoseconcentration of the patient for one unit of insulin. In FIG. 2, the 40mg/dl increase corresponds to an under-delivery of basal insulin. Theunder-delivery may be due to the basal rate being too low or due to anincreased demand from the patient during that time of day. The 80 mg/dldecrease corresponds to an over-delivery of basal insulin.

To calculate the amount under-delivered, the insulin calculation module120 divides the increase in blood glucose level (+40 mg/dl) by thecorrection factor of the patient to determine the amount of insulinrequired to lower the blood glucose level to the target blood glucosebaseline 215. This is the amount of insulin that was under-delivered tothe patient during the basal rate test. Assume in the example of FIG. 2that the patient's correction factor is one unit per 40 mg/dl. In thiscase, a correction bolus of one unit of insulin would decrease thepatient's blood glucose level to the blood glucose baseline. Tocalculate the amount of insulin over-delivered, the insulin calculationmodule 120 divides the decrease in blood glucose level (−80 mg/dl) bythe correction factor of the patient (1 u per 40 mg/dl). Thiscorresponds to a correction bolus of −2 units of insulin, i.e., theamount of insulin delivered needs to be reduced by 2 units of insulin.

The under-delivered or over-delivered amount can be used to recommendchanges to the basal rate pattern. In the example of FIG. 2, the insulincalculation module 120 may determine that the existing basal ratepattern 220 needs to be increased at some point by one unit of insulinto address the 40 mg/dl increase and decreased at some point by 2 unitsof insulin to address the 80 mg/dl decrease.

The BG management device 100 is more valuable if recommended changesanticipate an under-delivery or over-delivery. However, anticipatingwhen to change the basal rate is complicated by a delay, or a lag time,in insulin uptake before the insulin becomes effective. Anothercomplication is that the lag time may be different for glucose levelsmeasured using blood and glucose levels measured using interstitialfluid. Measuring blood glucose concentration using the interstitialfluid may make the uptake appear to have additional lag time. In someembodiments, the insulin calculation module 120 recommends a change in abasal rate that precedes any actual times of under-delivery orover-delivery by a time duration that compensates for a lag timeassociated with the subcutaneous insulin delivery and with the glucosemeasurement method.

In some embodiments, in addition to the uptake lag time, the insulincalculation module 120 uses the time from a beginning of a change in theblood glucose level to a change in direction of the blood glucose datavalues to determine a recommended change to the basal insulin ratepattern 220. In the example of FIG. 2, it is determined that one unit ofinsulin is needed to correct the under-delivery of insulin resulting inthe 40 mg/dl increase in blood glucose level. The increase began at t₃and a change in direction occurred two hours later at t₅. The insulincalculation module 120 may recommend a change that includes adding oneunit of insulin to the basal rate pattern 220 and spreading the deliveryout over two hours corresponding to the change in direction time, i.e.,a rate of 0.5 u/hr. This shown by the basal rate increase 225 of 0.5u/hr for two hours over time t₁ to t₂. The time t₁ is shifted earlierthan the time of the increase at t₃ by a time duration to compensate fora delay in the insulin uptake so that the insulin may act on the bloodglucose.

Also in FIG. 2, an over-delivery of 2 units of insulin resulted in an 80mg/dl increase in blood glucose level. The decrease began at t₅ and achange in direction occurred six hours later at t₇. The insulincalculation module 120 may recommend a change that includes subtractingtwo units of insulin from the basal rate pattern 220 over six hours at arate of 0.33 u/hr. This shown by the basal rate decrease 230 of 0.33u/hr for six hours over time t₂ to t₆. The time t₂ is early enough tocompensate for the delay in insulin uptake.

The lag time for insulin uptake may depend on several factors. In someembodiments, the insulin calculation module 120 determines a timeduration to compensate for such a time lag using the type of insulindelivered. Some insulin types have a faster uptake than other types, andthe insulin calculation module 120 may use a table stored in a memory ofthe BG management device to correlate a time duration to an insulintype. In some embodiments, the insulin calculation module 120 calculatesthe compensating time duration using an activity level of the patientand/or the fitness level of the patient. In some embodiments, thecompensating time lag is pre-determined from clinical studies and isstored in a memory for use by the insulin calculation module 120.

In some embodiments, the insulin calculation module 120 may adjust thecorrection factor before determining an amount of insulin under orover-delivered. In certain embodiments, the insulin calculation module120 may use a correction factor multiplier to adjust the correctionfactor when determining the amount of insulin under or over-delivered,and consequently adjusting the amount of insulin in any recommendedchanges to the basal rate pattern 220. For example, assume as in FIG. 2that the patient's correction factor is one unit per 40 mg/dl. If thecorrection factor multiplier is 1.3, the insulin calculation module usesa correction factor of one unit per 52 mg/dl [(1.3)(40 mg/dl/unit)]. Forthe 40 mg/dl increase in FIG. 2, the insulin calculation module 120divides the increase in blood glucose level (40 mg/dl) by the correctionfactor of the patient (1 u per 52 mg/dl). This corresponds to acorrection bolus of 0.77 units [(40)/(52)] of insulin. The insulincalculation module 120 may recommend adding 0.39 u/hr for two hours tothe basal rate pattern.

Using a correction factor multiplier results in a lower amount of basalinsulin allowing adjustments to be made more safely made. This may givea user more confidence in using the recommended changes to the basalrate pattern 220. The 80 mg/dl decrease corresponds to a correctionbolus of 1.54 units of insulin. The insulin calculation module 120 mayrecommend subtracting 0.26 u/hr for six hours to the basal rate pattern.The controller 115 may store the correction factor multiplier in amemory. The correction factor multiplier may be manually set orprogrammed by a clinician. The clinician may set the correction factormultiplier to a value that accords to a level of confidence or comfortto the clinician in the recommended changes to the basal rate pattern220.

In some embodiments, if the blood glucose data received during the basalrate test indicates that the blood glucose level of the patient isoutside of a specified range of blood glucose levels, the controller 115cancels the basal insulin rate test. If the blood glucose level is abovethe range, the controller 115 may recommend a correction bolus to betaken by the patient. The insulin calculation module 120 calculates theamount of insulin in the correction bolus by dividing the blood glucoseconcentration by the specified correction factor for the patient.

If the blood glucose level is below the range, the controller 115 mayrecommend an amount of carbohydrates to be eaten by the patient. Theinsulin calculation module 120 calculates the amount of carbohydratesusing a correction factor specified for the patient and a carbohydrateratio specified for the patient. A carbohydrate ratio refers to theamount of carbohydrates reduced, or covered, by a unit of insulin.

For example, assume that at the beginning of a basal rate test, theblood glucose level of a patient is 40 mg/dl below the specified rangeand the specified correction factor is 1 unit per 80 mg/dl. The insulincalculation module 120 determines that −0.5 units of insulin (−40/80)are required to bring the blood glucose level back within the specifiedrange. Negative insulin cannot be delivered so this corresponds to arequirement for carbohydrates. Assume that the carbohydrate ratio of thepatient is 20 grams of carbohydrates per unit of insulin (20 g/u). Theinsulin calculation module 120 multiplies the amount of insulin by thecarbohydrate ratio to determine that the patient should eat 10 grams ofcarbohydrates [(0.5)(20)]. The insulin calculation module 120 may takeinto account additional factors such as the health status of the patientand the activity level of the patient in recommending the carbohydrateamount. In some embodiments, if the blood glucose of the patient isoutside the specified range of blood glucose levels, the controller 115suspends the start of the basal insulin rate test until the bloodglucose of the patient is within the specified range of blood glucoselevels.

As discussed previously, appropriate basal rates may differ for apatient throughout the course of a day. The BG management device 100 mayinclude a timer circuit 117 operatively coupled to the controller 115.The controller 115 displays user instructions to execute a basal ratetest at one or more specified times during a day. In some embodiments,controller 115 displays user instructions to run the basal insulin ratetest on multiple days. The controller 115 may prompt the user to run thetest during substantially the same time on the multiple days. This mayresult in more appropriate basal delivery rates being used at differenttimes during the day.

It is often difficult to maintain a stable blood glucose target valueovernight because the correction factor varies as a function of time. Inorder to stabilize the glucose value at a target blood glucose value,the basal rate may often be adjusted during overnight periods tocompensate for changes in the correction factor. An insulin pump usermay go through several iterations of trial and error while attempting tofind appropriate overnight basal rates. A trial and error method mayresult in less than optimal control of overnight blood glucose level.

According to some embodiments, the BG management device 100automatically executes a basal rate test during a period when foodintake is restricted, such as overnight for example. The basal rate testmay start a specified time after a user prompts the BG management device100 to execute the basal rate test. For example, if the period isovernight, the user prompt may start a timer circuit and the controller115 may initiate the overnight basal rate test when a time durationexpires. The insulin calculation module 120 automatically determines oneor more basal rates for a basal rate profile using a basal ratecalibration and verification technique. The basal blood glucose value gcan be approximated by

g(t)≅c(t)b(t−τ),  (1)

where c(t) is the basal correction factor, b(t) is the basal insulinrate, and τ is the delay or lag time associated with the uptake of asubcutaneous infusion of insulin. Food consumption and exercise areassumed to be negligible during the period of the test.

The insulin calculation module 120 may perform a rapid calibration thatcan be executed during a period as short as two time periods, such astwo nights for example. The correction factor c(t) may vary as afunction of time. To determine c(t), blood glucose data values g₁(t) andbasal insulin delivery rates b/(t) are recorded periodically throughouta first observation period. Rewriting Equation (1) to solve for c(t) forthe first period yields

$\begin{matrix}{{{c_{1}(t)} = \frac{g_{1}(t)}{b_{1}( {t - \tau_{1}} )}}.} & (2)\end{matrix}$

The delay for insulin uptake τ₁ can be an assumed value based on currentestimates from clinical studies that use that type of insulin, or can bedetermined on a per patient basis using stochastic or deterministic timeseries analysis of prior or current basal test data. The time seriesanalysis of the blood glucose data values may be performed under pulsefunction, step function, or continuous changes in insulin delivery. Thetime-dependent changes in insulin delivery may be present in the user'scurrent basal profile or the user may be prompted to create atime-dependent change by the insulin calculation module. The stochasticor deterministic time series analysis can be performed on blood glucosedata obtained from previous calibration or observation periods, such asprevious nights for example. Thus, the delay for insulin uptake may bedetermined using blood glucose data obtained prior to the basal ratetest.

A desired target blood glucose value g_(t)(t) may be a constant or afunction of time. Equation (1) can be written as

g _(t)(t)≅c ₁(t)b _(t)(t−τ ₁),  (3)

where c₁(t) is the correction factor determined from the first period ofdata values from Equation (2). Solving equation (3) for a controllingbasal insulin rate b_(t)(t) that achieves the desired g_(t)(t) yields

$\begin{matrix}{{b_{t}(t)} = {\frac{g_{t}( {t + \tau_{1}} )}{c_{1}( {t + \tau_{1}} )}.}} & (4)\end{matrix}$

It is assumed that the correction factor c(t) is a periodic functionthat repeats on a twenty four hour cycle, and that c(t) determined fromdata and basal rates during the first period of reduced food intake willbe similar on subsequent periods twenty-four hours later.

During the second period of observation, blood glucose data values g₂(t)and basal rates b₂(t) are again recorded periodically. Ideallyg₂(t)=g_(t)(t), but in reality g₂(t)=g_(t)(t)+ε(t), where ε(t) is theresidual deviation from the target blood glucose value. Thus, Equation(1) can be written as

g _(t)(t)+ε(t)=c ₁(t)b ₁(τ₁−δ)),  (5)

Assuming that ε(t) is primarily due to the error in the estimate of τ₇,Equation (5) can be rewritten as

g _(t)(t)+ε(t)=c ₁(t)b _(t1)(t−(τ₁−δ)),  (6)

where δ is the error in the delay estimate. Combining Equations 5 and 6gives

ε(t)=c ₁(t)[b _(t)(t−τ ₁)−b _(t)(t−(τ₁−δ))].  (7)

Curve fitting or other standard minimization techniques can be used todetermine the most appropriate estimate of δ to satisfy Equation (7).Once 6 is determined, the control estimate for the basal insulindelivery rate or rates b_(t)(t) that achieves the desired blood glucosetarget g_(t)(t) can be written as

$\begin{matrix}{{{b_{t}(t)} = \frac{g_{t}( {t + \tau_{2}} )}{c_{1}( {t + \tau_{2}} )}},} & (8)\end{matrix}$

where τ₂=τ₁−δ. The insulin calculation module may then recommend changesto the t basal rate pattern using b_(t)(t).

The rapid calibration technique is a method to quickly achieve improvedcontrol over blood glucose level. In some embodiments, the insulincalculation module 120 executes a basal rate test that uses ageneralized calibration technique to achieve more accurate estimates ofb_(t)(t). The generalized calibration method uses least squaresestimation techniques with at least two periods of observing bloodglucose data and basal insulin delivery rates. Referring back toEquation (1) and with g(t) and b(t) measured over several periods, τ andc(t) can be estimated by curve fitting with a finite order polynomial oran orthogonal series approximation such as a Fourier seriesapproximation for example. The resulting estimate of b_(t)(t) iscalculated using Equation 3 with τ and c(t) estimated from the curve fitresults.

According to some embodiments, the BG management device includes aninsulin pump. FIG. 3 is a block diagram of portions of an example of aBG management device 300 that includes a pump mechanism 330 to deliverinsulin to the patient. The pump mechanism 330 is operatively coupled tothe controller 115. The controller 115 may track the amount of insulindelivered via the pump mechanism 330. The BG management device 300includes a memory 116 operatively coupled to the controller 115 to storeone or more basal rate patterns 325. The BG management device deliversbasal insulin according to the basal rate patterns. The BG managementdevice 300 also may deliver insulin through boluses such as a correctionbolus or a carbohydrate bolus. In some embodiments, the BG managementdevice 300 has a timer circuit 117 that includes a real time clockcoupled to the controller 115. The controller 115 is configured to varya basal rate of insulin delivery by a time of day according to a basalrate pattern.

In some embodiments, the insulin calculation module 120 is able to keeptrack of the amount of active insulin in the patient. This is sometimesreferred to as insulin on board (IOB). To track the amount of activeinsulin, the controller 115 uses the amount of insulin delivered, thetime that elapsed since delivery of insulin and a duration of how longthe insulin is active in the blood. The duration may be determined usingkinetic action, which is the time it takes for insulin to disappear fromthe blood, or the duration of insulin action (DIA), which is how longthe insulin lowers blood glucose. In some embodiments, the controller115 cancels a basal rate test if the insulin calculation module 120determines that the active insulin amount is above a specified thresholdinsulin amount. This minimizes the risk of IOB confounding the resultsof the basal rate test.

In some embodiments, the controller 115 cancels the basal insulin ratetest if the controller 115 determines that an insulin bolus dose, suchas a correction insulin bolus or a carbohydrate insulin bolus, isdelivered during the basal insulin rate test. In some embodiments, ifthe user enables an insulin bolus delivery, the controller 115 displaysa warning that the basal insulin test will be canceled if the userelects to proceed with delivery of the insulin bolus dose.

FIG. 4 is an illustration of a BG management device 400 that includes aninsulin pump. The BG management device 400 includes a cassette orcartridge of insulin and tubing 440 connectable to a patient such as bya Luer lock 445. The BG management device 400 includes a user interfacethat may include a display 402 operatively coupled to a controller 115.The user interface may also include one or more keys 404.

Returning to FIG. 3, the blood glucose data obtained during the basalinsulin rate test may be produced by a second device separate from theBG management device 300. The controller 115 displays user instructionsfor the basal rate test. The user interface 105 and the input 110 areconfigured to receive the sampled blood glucose data entered manually bythe user through the user interface 105. The controller 115 mayperiodically prompt the user to enter a blood glucose value at differenttimes during the test, or to enter the blood glucose data all at onceafter the test.

FIG. 5 is another block diagram of portions of a BG management device500 that includes a pump mechanism 530 and delivers basal insulinaccording to one or more basal rate patterns 525 stored in memory 116. Ablood glucose monitor, or GM 550, is communicatively coupled to theinput 110. The input 110 is configured to receive the sampled bloodglucose data from the GM 550. In some examples, the GM 550 is includedin the BG management device 500 and is coupled to the input 110. In someexamples, the GM 550 is included in a second device. The input 110 mayreceive the blood glucose data during the basal rate test or after thetest is run. The input 110 may include a communication port, such ascommunication port 447 located on the rear face of the device in FIG. 4,and the GM 550 is communicatively coupled to the input 110 by thecommunication port 447. In some embodiments, the communication port 447is a wired port such as a serial interface or bus interface forcommunicating with the second device. In some embodiments, thecommunication port 447 is a wireless port such as an infrared (IR)communication port or a radio frequency (RF) communication port. Theinput 110 wirelessly receives the sampled blood glucose data from thesecond device.

Returning to FIG. 5, in some embodiments, the GM 550 is a continuous GMand automatically collects the sampled blood glucose data. For example,the GM 550 may include a blood glucose sensor. The blood glucose sensorproduces a blood glucose signal representative of a blood glucose levelof the patient. The GM 550 samples the blood glucose signal to obtainthe sampled blood glucose data.

In some embodiments, the GM 550 may need to prompt the user to begin ablood glucose measurement. For example, the GM 550 may require diabetestest strips to take a blood glucose measurement. The controller 115prompts the user, via a display, to begin a blood glucose measurementusing the GM 550. The user then provides a new test strip to the GM 550when prompted during the basal rate test. In another example, the GM 550may include a drum of diabetes test strips and the user advances thedrum to a fresh or unused test strip when prompted by the controller115. The controller 115 may display a recommended basal rate after thebasal rate test. The controller 115 may also communicate a recommendedchange in the basal rate to the second device via a communication port.

According to some embodiments, the BG management device is a GM. FIG. 6is a block diagram of a BG management device 600 that includes a bloodglucose sensor circuit 635 operatively coupled to the input 110. Theblood glucose sensor circuit 635 produces a blood glucose signalrepresentative of a blood glucose level of the patient and provides thesampled blood glucose data to input 110. In some embodiments, the bloodglucose sensor circuit 635 includes an implantable blood glucose sensor.In some embodiments, the blood glucose sensor includes a percutaneousblood glucose sensor. The blood glucose sensor circuit 635 may includesignal conditioning circuits, such as for signal filtering and signalamplification for example. If an implantable blood glucose sensor isused, the blood glucose sensor circuit 635 may include a communicationcircuit configured to receive blood glucose data wirelessly, such as byRF communication.

The BG management device 600 includes a second input 630 communicativelycoupled to the controller 115. The second input 630 receives informationrelated to basal insulin delivery, such as one or more basal ratepatterns used during the basal rate test. The information related toinsulin delivery may be received into a memory 116. The insulincalculation module 120 determines at least one of an amount of insulinover-delivered and an amount of insulin under-delivered during the basalrate test using the insulin delivery information and the sampled bloodglucose data. The BG management device 600 may include a communicationport 647 coupled to the second input 630. The communication port 647receives the information related to insulin delivery from a seconddevice. In some embodiments, the communication port 647 is a wired portsuch a serial interface or bus interface. In some embodiments, thecommunication port 647 is a wireless port such as an infrared (IR)communication port or a radio frequency (RF) communication port. Thesecond input 630 wirelessly receives the insulin delivery data from thesecond device. As an example, the second device may be an insulin pump.The insulin calculation module 120 may determine changes to the basalrate pattern used to deliver basal insulin during the basal rate test.The controller 115 communicates recommended changes through thecommunication port 647 or may display the recommended changes on adisplay.

In some embodiments, the user interface 105 and the second input 630 areconfigured to receive the information related to insulin delivery by auser manually entering the information through the user interface 105.The insulin delivery information may be obtained from a pump forexample. The controller 115 may display any recommended changes to thebasal rate pattern.

FIG. 7 is a block diagram of portions of another example of a BGmanagement device 700. BG management device 700 includes neither a GMnor an insulin pump. The BG management device 700 includes a userinterface 105, an input 110, and a controller 115 communicativelycoupled to the input 110 and the user interface 105. The input 110includes at least one communication port 747 configured for receivingsampled blood glucose information. The communication port 747 mayprovide a wired connection to a second device, or the communication port747 may provide a wireless connection to a second device. The sampledblood glucose information may include at least one time-stamp in orderto align the sampled blood glucose information to information related toinsulin delivery.

The insulin delivery information may be received through the samecommunication port 747 or a second communication port. The communicationports may be any combination of wired or wireless communication ports.The insulin delivery information includes information related to basalinsulin delivered according to a basal rate pattern, and may include atleast one time-stamp to align the insulin delivery information with theblood glucose information. The insulin calculation module 120 determinesat least one of an amount of insulin over-delivered and an amount ofinsulin under-delivered during the basal rate test using the insulindelivery information and the sampled blood glucose data. The insulincalculation module 120 may recommend changes to the basal rate pattern.The controller 115 may communicate recommended changes to the basal ratepattern through the communication port 747 and/or the controller 115 maydisplay the recommended changes.

Method Embodiments

FIG. 8 is a flow diagram of a method 800 of using a BG management deviceto execute a basal rate test. At block 805, a user prompt is received ina BG management device to start a basal insulin rate test. The userinterface may include a push-button, keypad, or mouse. The userinterface may also include a display to display one or more instructionsfor the user to execute the basal rate test, and to display to displayany recommend changes to a basal rate or a basal rate pattern. In someembodiments, the method 800 includes displaying instructions for thebasal insulin rate test using the BG management device.

At block 810, sampled blood glucose data is received in the BGmanagement device. The blood glucose data is obtained from a patientduring a specified time duration, including a time during delivery ofinsulin according to a basal insulin rate pattern that is part of thebasal rate test.

At block 815, at least one of an amount of basal insulin over-deliveredor an amount of basal insulin under-delivered is determined. Theover-delivery and/or under-delivery occur in trying to meet a targetblood glucose baseline during the basal insulin rate test. In someembodiments, the method 800 includes the BG management deviceautomatically recommending changes, if any, to the basal insulin ratepattern.

In some embodiments, the method 800 includes determining an amount ofbasal insulin over-delivered or an amount of basal insulinunder-delivered using the correction factor and the variance from theblood glucose baseline concentration. In some embodiments, the amount ofinsulin over or under-delivered is determined using an adjustedcorrection factor. The correction factor may be adjusted using acorrection factor multiplier. In some embodiments, recommending a changemay include spreading out the change to the basal delivery rate patternout over a time duration corresponding to a time to a change indirection of the blood glucose data values.

In some embodiments, the method includes recommending changes to thebasal insulin rate pattern that precede any actual times ofover-delivery or under-delivery by a time duration that compensates fora delay or lag time associated with subcutaneous insulin delivery. Insome embodiments, the method 800 includes calculating the lag time usingat least one of i) the type of insulin delivered during the basal ratetest, ii) the activity level of the patient at the time the basal ratetest takes place, iii) the fitness level of the patient, and iv) themethod of obtaining the blood glucose data, e.g., whether the bloodglucose data was obtained from blood or from interstitial fluid. In someembodiments, the method 800 includes calculating the lag time usingblood glucose data obtained prior to the basal insulin rate test.

According to some embodiments, the BG management device includes aninsulin pump. The method 800 includes determining an amount of activeinsulin (IOB) at the beginning of the basal rate test. The IOB may bedetermined before delivering basal insulin according to a basal ratepattern of the basal insulin test. In some embodiments, if an amount ofactive insulin is above a specified threshold active insulin amount, theBG management device may cancel the basal rate test. In someembodiments, the method 800 includes canceling the basal insulin ratetest if an insulin bolus dose, such as a correction bolus or acarbohydrate bolus, is delivered during the basal insulin rate test.

According to some embodiments, the BG management device includes aninsulin pump and a GM. The method 800 includes automatically receivingthe sampled blood glucose data from the blood glucose monitor. In someembodiments, the BG management device includes the insulin pump and theblood glucose data is obtained using a separate device. The method 800includes receiving the sampled blood glucose data into the BG managementdevice from the separate device through a communication port. Thecommunication port may be a wireless port or a wired port. The separatedevice may be a continuous GM.

In some embodiments, the separate device may be a GM that requires someaction by the user to obtain a blood glucose reading. For example, theGM may require the user to place a test strip into the GM in order toobtain a glucose reading. In some embodiments, the method 800 mayinclude prompting the user through a user interface to obtain bloodglucose data using the separate device. The prompting may be periodicduring the basal rate test.

In some embodiments, the blood glucose data obtained from the separatedevice is entered manually into the BG management device. The method 800includes the BG management device receiving the blood glucose datathrough the user interface. The user interface is configured for manualentry of blood glucose data, such as by including a keypad and adisplay. The user reads the blood glucose data from the separate GM andmanually enters the blood glucose data into the BG management device. Insome embodiments, the method 800 includes the BG management deviceperiodically prompting the user to manually enter a blood glucose valueduring the basal rate test.

According to some embodiments, the BG management device includes a GMand does not include an insulin pump. The basal insulin is deliveredaccording to a basal rate pattern using a second separate device. Thesampled blood glucose data is received automatically using the includedGM. The method 800 further includes receiving information related toinsulin delivery into the BG management device from the separate device,including an amount of insulin delivered according to the basal ratepattern. The BG management device determines at least one of an amountof insulin over-delivered and an amount of insulin under-deliveredduring the basal rate test using the insulin delivery information andthe sampled blood glucose data.

In some embodiments, the method 800 includes receiving the insulindelivery information into the BG management device through acommunication port. As part of the basal rate test, the BG managementdevice may communicate a recommended change to the basal rate pattern tothe separate device using the communication port. This is useful if theseparate device is an insulin pump. In some embodiments, the method 800includes receiving the insulin delivery information into the BGmanagement device by manually entering the insulin delivery information.The information is manually entered via a user interface on the BGmanagement device. Any recommended changes to the basal rate pattern maybe displayed on the BG management device.

According to some embodiments, the BG management device does not includea GM or an insulin pump. The basal insulin is delivered according to abasal rate pattern using a second separate device, such as an insulinpump for example. The method 800 includes providing insulin deliveryinformation, such as an amount of insulin delivered according to thebasal rate pattern, to the BG management device using the second device.

The BG management device receives sampled blood glucose data from thesecond separate device or a third device. At least one of the insulindelivery information and the sampled blood glucose data includes atime-stamp to allow for alignment of the insulin delivery informationand the blood glucose data. For example, the time-stamp for the insulindelivery may be the time at which the basal rate changes. The BGmanagement device determines at least one of an amount of insulinover-delivered and an amount of insulin under-delivered during the basalrate test using the insulin delivery information and the sampled bloodglucose data. Any recommended changes to the basal rate pattern may bedisplayed on the BG management device.

In some embodiments, the method 800 includes executing the basal insulinrate test during a substantially same time on multiple days. In someexamples, the method 800 includes executing an overnight basal ratetest. In some examples, the method includes executing an overnight basalrate test that includes an overnight basal rate calibration andverification technique.

FIG. 9 is a flow diagram of another method 900 of using a BG managementdevice to execute a basal rate test. At block 905, sampled blood glucosedata is received in a BG management device. The blood glucose data maybe obtained from a patient during a specified time duration according toa specified basal insulin rate pattern that is part of the basal ratetest. At block 910, a time varying correction factor c(t) is determinedusing the sampled blood glucose data and the specified basal insulinrate pattern. At block 915, a time varying basal rate pattern b(t) isdetermined. The time varying basal rate pattern is to achieve the targetblood glucose baseline. The target blood glucose baseline may be aconstant or a time varying function g(t). In some embodiments, themethod 900 includes generating a change to the test-specified basal ratepattern using the determined time varying basal rate pattern b(t). Insome embodiments, the method includes recommending a change to thetest-specified basal rate pattern, such as by using a display forexample.

The accompanying drawings that form a part hereof, show by way ofillustration, and not of limitation, specific embodiments in which thesubject matter may be practiced. The embodiments illustrated aredescribed in sufficient detail to enable those skilled in the art topractice the teachings disclosed herein. Other embodiments may beutilized and derived therefrom, such that structural and logicalsubstitutions and changes may be made without departing from the scopeof this disclosure. This Detailed Description, therefore, is not to betaken in a limiting sense, and the scope of various embodiments isdefined only by the appended claims, along with the full range ofequivalents to which such claims are entitled.

Such embodiments of the inventive subject matter may be referred toherein, individually and/or collectively, by the term “invention” merelyfor convenience and without intending to voluntarily limit the scope ofthis application to any single invention or inventive concept if morethan one is in fact disclosed. Thus, although specific embodiments havebeen illustrated and described herein, it should be appreciated that anyarrangement calculated to achieve the same purpose may be substitutedfor the specific embodiments shown. This disclosure is intended to coverany and all adaptations, or variations, or combinations of variousembodiments. Combinations of the above embodiments, and otherembodiments not specifically described herein, will be apparent to thoseof skill in the art upon reviewing the above description.

The Abstract of the Disclosure is provided to comply with 37 C.F.R. §1.72(b), requiring an abstract that will allow the reader to quicklyascertain the nature of the technical disclosure. It is submitted withthe understanding that it will not be used to interpret or limit thescope or meaning of the claims. In addition, in the foregoing DetailedDescription, it can be seen that various features are grouped togetherin a single embodiment for the purpose of streamlining the disclosure.This method of disclosure is not to be interpreted as reflecting anintention that the claimed embodiments require more features than areexpressly recited in each claim. Rather, as the following claimsreflect, inventive subject matter lies in less than all features of asingle disclosed embodiment. Thus the following claims are herebyincorporated into the Detailed Description, with each claim standing onits own.

What is claimed is:
 1. An apparatus comprising: a user interfaceconfigured to generate an electrical signal to start a basal insulinrate test when prompted by a user; an input configured to receivesampled blood glucose data of a patient that is obtained during aspecified time duration, including a time duration when insulin isdelivered according to a specified basal insulin rate pattern; and acontroller communicatively coupled to the input and the user interface,the controller including an insulin calculation module, wherein theinsulin calculation module is configured to determine at least one of anamount of basal insulin over-delivered and an amount of basal insulinunder-delivered during the basal insulin rate test in trying to meet atarget blood glucose baseline.
 2. The apparatus of claim 1, wherein theinsulin calculation module is configured to determine the over-deliveredamount and the under-delivered amount using a correction factor of thepatient and a variance of a blood glucose level from the target bloodglucose baseline.
 3. The apparatus of claim 2, wherein the insulincalculation module is configured to determine the over-delivered amountand the under-delivered amount using an adjusted correction factor ofthe patient.
 4. The apparatus of claim 2, wherein the insulincalculation module is configured to determine a recommended change, ifany, to the basal insulin rate pattern.
 5. The apparatus of claim 4,wherein the recommended change precedes any actual time of over-deliveryor under-delivery by a time duration that compensates for a lag timeassociated with subcutaneous insulin delivery.
 6. The apparatus of claim4, wherein the user interface includes a display operatively coupled tothe controller, and wherein the controller is configured to display atleast one user instruction for the basal insulin rate test.
 7. Theapparatus of claim 6, wherein the controller is configured to display arecommended change to a basal insulin rate pattern.
 8. The apparatus ofclaim 4, including: a pump mechanism configured to deliver insulinaccording to the specified basal insulin rate pattern; and a memory tostore at least one basal insulin rate pattern, wherein the pumpmechanism and the memory are operatively coupled to the controller. 9.The apparatus of claim 8, including a blood glucose monitorcommunicatively coupled to the input.
 10. The apparatus of claim 9,wherein the blood glucose monitor is a continuous blood glucose monitorconfigured to automatically collect the sampled blood glucose data. 11.The apparatus of claim 10, including: a display operatively coupled tothe controller, and wherein the controller is configured to prompt theuser, via the display, to begin a blood glucose measurement using theblood glucose monitor.
 12. The apparatus of claim 8, wherein the userinterface and the input are configured to receive the sampled bloodglucose data entered manually by the user.
 13. The apparatus of claim12, including: a display operatively coupled to the controller, whereinthe controller is configured to display user instructions for the basalrate test, including periodically prompting the user to enter a bloodglucose value.
 14. The apparatus of claim 8, wherein the insulincalculation module is configured to determine an amount of activeinsulin in the patient and to cancel the basal insulin rate test if theactive insulin amount is above a specified threshold insulin amount. 15.The apparatus of claim 8, wherein the controller is configured todetermine whether an insulin bolus dose is delivered and to cancel thebasal insulin rate test if it determines that an insulin bolus dose isdelivered during the basal insulin rate test.
 16. The apparatus of claim8, including a real time clock coupled to the controller, wherein thecontroller is configured to vary a basal rate of insulin delivery by atime of day according to the basal rate pattern.
 17. The apparatus ofclaim 4, wherein the input is a first input and the apparatus furtherincludes: a blood glucose sensor circuit operatively coupled to thefirst input, the blood glucose sensor circuit configured to produce ablood glucose signal representative of a blood glucose level of thepatient and provide the sampled blood glucose data to the first input; asecond input communicatively coupled to the controller, wherein thesecond input is configured to receive information related to insulindelivery according to the basal rate pattern, and wherein the insulincalculation module is configured to determine at least one of the amountof basal insulin over-delivered and the amount of basal insulinunder-delivered using the insulin delivery information and the sampledblood glucose data.
 18. The apparatus of claim 17, including acommunication port communicatively coupled to the second input, thecommunication port to receive the information related to insulindelivery.
 19. The apparatus of claim 18, wherein the controller isconfigured to communicate a recommended change to the basal rate patternthrough the communication port.
 20. The apparatus of claim 17, whereinthe user interface and the second input are configured to receive theinformation related to insulin delivery that is entered manually by theuser.